Use of DHEA derivatives on keratinous substances

ABSTRACT

Methods of improving the appearance of keratinous substances using at least one DHEA derivative such as the skin, hair, eyelashes and/or nails, in particular for preventing or treating cutaneous signs of ageing and/or a faded complexion and/or disorders of pigmentation of the skin or hair and/or drying of the skin and/or hyperseborrhoea and/or imperfections relating to hyperseborrhoea and/or sensitive skin and/or dandruff and/or hair loss and/or canities.

FIELD OF THE INVENTION

[0001] The present invention relates to the use of at least one DHEAderivative for improving the appearance of keratinous substances, suchas the skin, hair, eyelashes and/or nails, in particular for preventingor treating cutaneous signs of ageing and/or a faded complexion and/ordisorders of pigmentation of the skin or hair and/or drying of the skinand/or hyperseborrhoea and/or imperfections related to hyperseborrhoeaand/or sensitive skin and/or dandruff and/or hair loss and/or canities.

[0002] The present invention also relates to a process for the treatmentof keratinous substances comprising the topical application to thekeratinous substances of a composition including at least one DHEAderivative in a physiologically acceptable medium.

BACKGROUND OF THE INVENTION

[0003] DHEA or dehydroepiandrosterone is a natural steroid producedessentially by the corticoadrenal glands. Exogenous DHEA, administeredtopically or orally, is known for its ability to promote keratinizationof the epidermis (JP-07 196 467) and to treat dry skin by increasing theendogenous production and secretion of sebum, thus strenghtening thebarrier effect of the skin (U.S. Pat. No. 4,496,556). It has also beendisclosed, in U.S. Pat. No. 5,843,932, to use DHEA for curing atrophy ofthe dermis by inhibition of the loss of collagen and of connectivetissue. Finally, the ability of DHEA to control the papery appearance ofthe skin (FR 00/00349), to adjust the pigmentation of the skin and hair(FR 99/12773) and to combat atrophy of the epidermis (FR 00/06154) hasbeen demonstrated. These properties of DHEA make it a candidate ofchoice as an antiageing active principle.

[0004] However, DHEA exhibits effects of a hormonal nature which canrender its use problematic.

[0005] For this reason, attempts have been made to make available DHEAderivatives which exhibit similar advantageous properties to DHEA butwhich do not have hormonal effects.

[0006] DHEA derivatives already known include 3β-acetoxy-7-oxo-DHEA orΔ5-androstene-3β-acetoxy-7,17-dione, which has been disclosed as beingeffective in the modulation of the immune system (U.S. Pat. Nos.5,292,730, 5,585,371, 5,641,766), the treatment of Alzheimer's disease(U.S. Pat. No. 5,707,983), the treatment of HIV syndrome (U.S. Pat. No.5,885,977) and for promoting weight loss (U.S. Pat. Nos. 5,296,481,5,807,848).

[0007] PCT patent application WO 99/25333 additionally mentions the use,in particular the topical use, of 3β-acetoxy-7-oxo-DHEA in theprophylactic and curative treatment of lupus erythematosus, which is adisorder of the immune system capable of affecting several organs andwhich is revealed in the skin by a transverse redness of the face and/orby squamous erythemal plaques disseminated over the body.

[0008] U.S. Pat. No. 5,424,463 discloses 7-keto-DHEA (orΔ5-androstene-3β-ol-7,17-dione) and its hydrolysable derivativesobtained by modification of the 3β-hydroxy group, the derivatives beingcapable of restoring 7-keto-DHEA after hydrolysis. The 3β-hydroxy groupis converted to carbamate or is esterified with (i) a saturated orunsaturated and normal or branched C₂-C₂₂ aliphatic acid, (ii) a C₇-C₂₂aromatic acid, (iii) a dicarboxylic acid comprising 3 or more carbonatoms, for which only one carbonyl group is esterified with the3-hydroxy group of the steroid, or (iv) an inorganic acid, such assulphuric acid and phosphoric acid. U.S. Pat. No. 5,424,463 discloses7-keto-DHEA and its hydrolysable derivatives as being effective inpromoting weight loss.

[0009] PCT patent application WO 98/40074 discloses the use of DHEAderivatives of formula (A):

[0010] in which:

[0011] R₁ is chosen from: a hydrogen atom or the following functionalgroups: ester of organic acid comprising 1 to 24 carbon atoms, sulphuricester or phosphoric ester, or carbonaceous ether comprising 1 to 24carbon atoms comprising no or several nitrogen atoms, or ethers ofcarbohydrates comprising 3 to 100 carbon atoms and their derivativescomprising or not comprising one or more nitrogen atoms;

[0012] R₂ is chosen from: a hydrogen atom or an ester functional groupof fatty acid comprising 1 to 24 carbon atoms;

[0013] R₃ is chosen from: a hydrogen atom, an —OH group or groups offormulae: —CO—R₄, —CHOH—R₄, ═CH—CH₃, ═COH—CH₃, —CHR₄—CH₃ or ═O, in whichgroups R₄ is an alkyl group comprising from 1 to 10 carbon atoms whichis or is not substituted; in a composition for preventing or treatingsigns of cutaneous ageing and/or the effects of UV radiation on theskin.

[0014] PCT patent application WO 00/28996 discloses a composition forimproving the texture of tissues comprising a DHEA derivative of formula(A) in combination with an elastin-derived peptide obtained by selectivecleavage of elastin by thermolysin.

[0015] However, to Applicants' knowledge, it has never been suggested touse DHEA derivatives of general formula (I) for improving the appearanceof keratinous substances, in particular in the treatment of signs ofageing.

SUMMARY OF THE INVENTION

[0016] The present invention relates to the use of at least one DHEAderivative for improving the appearance of keratinous substances, suchas the skin, hair, eyelashes and/or nails, in particular for preventingor treating cutaneous signs of ageing and/or a faded complexion and/ordisorders of pigmentation of the skin or hair and/or drying of the skinand/or hyperseborrhoea and/or imperfections related to hyperseborrhoeaand/or sensitive skin and/or dandruff and/or hair loss and/or canities.

[0017] The present invention also relates to a process for the treatmentof keratinous substances comprising the topical application to thekeratinous substances of a composition including at least one DHEAderivative in a physiologically acceptable medium.

DETAILED DESCRIPTION OF THE INVENTION

[0018] The present invention relates to the use, preferably the cosmeticuse, for improving the appearance of keratinous substances, of at leastone DHEA derivative of following formula (I):

[0019] in which:

[0020] R1 is chosen from:

[0021] a hydrogen atom;

[0022] a saturated or unsaturated, linear or branched, or cyclic, whichcan optionally comprise one or more heteroatoms, C₁-C₁₂ alkyl groupwhich is optionally substituted by one or more groups chosen from —OR′and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen and/orperfluoroalkyl and/or sulphate and/or phosphate and/or aryl and/orheterocycle, the heterocycle advantageously being chosen from an indole,a pyrimidine, a piperidine, a morpholine, a pyran, a furan, a piperazineor a pyridine;

[0023] an alkylcarbonyl group, the C₁-C₂₄ alkyl part of which issaturated or unsaturated, linear, branched or cyclic, and optionallysubstituted by one or more groups chosen from —OR′ and/or —SR′ and/or—COOR′ and/or —NR′R′ and/or halogen and/or perfluoroalkyl and/orsulphate and/or phosphate and/or aryl and/or heterocycle, theheterocycle advantageously being chosen from an indole, a pyrimidine, apiperidine, a morpholine, a pyran, a furan, a piperazine or a pyridine;

[0024] a phenyl group, optionally functionalized by one or more —OR′and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen and/orperfluoroalkyl and/or sulphate and/or phosphate and/or aryl and/orheterocycle groups;

[0025] a benzyl group, optionally functionalized by one or more —OR′and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen and/orperfluoroalkyl and/or sulphate and/or phosphate and/or aryl and/orheterocycle groups;

[0026] an arylcarbonyl group, preferably a phenylcarbonyl, or anarylalkylcarbonyl group, preferably a benzylcarbonyl, optionallysubstituted by one or more —OR′ and/or —SR′ and/or —COOR′ and/or —NR′R′and/or halogen and/or perfluoroalkyl and/or sulphate and/or phosphateand/or aryl and/or heterocycle groups;

[0027] an O═P(OH)OR′ group;

[0028] an (O)₂SOR′ group;

[0029] an (O)₂SR′ group;

[0030] a trialkylsilyl group (SiR₁₃) in which the R′ groups may beidentical or different;

[0031] an alkyloxycarbonyl group (R′OCO);

[0032] an alkylaminocarbonyl group (R′NR′′′CO);

[0033] a carbohydrate comprising 3 to 100 carbon atoms and theirderivatives;

[0034] R4 and R5:

[0035] together represent a group chosen from:

[0036] a keto group (═O);

[0037] a=CHR′ group;

[0038] an=NR′ group;

[0039] a=NCOR′ group;

[0040] each represent an identical —OR″ group;

[0041] advantageously the two —OR″ groups together form a 1,3-dioxolaneor 1,3-dioxane ring;

[0042] each represent an identical or different group chosen from:

[0043] a hydrogen atom;

[0044] an —NR′R′ group;

[0045] an —NHCOR′ group;

[0046] When R3 represents a hydrogen atom, R2 is chosen from:

[0047] an —OR6 group in which R6 has the same definitions as those givenabove for R1;

[0048] an amine group —N(R7)₂ in which the R7 substituents, which areidentical or different, have the same definitions as those given abovefor R1;

[0049] an N-sulphonamide group (—NR′′′SO₂R′) or an N-sulphonate group(—NR′′′SO₃R′), preferably in the alkali metal salt form;

[0050] a urea group (—NR′′′CONR′R′);

[0051] an alkylamide group (—NR′′′COR′);

[0052] an N-carbamate group (—NR′′′COOR′);

[0053] a thiol group (—SR′);

[0054] a thiophenyl group (—SPh);

[0055] a sulphone group (—SO₂R′);

[0056] a sulphoxide group (—SOR′);

[0057] a halogen;

[0058] an alkylsilane group (—SiR′₃) in which the R′ groups may beidentical or different;

[0059] R2 and R3 can also together represent a group chosen from:

[0060] a methylene (═CHR′);

[0061] an imine (═NHR′);

[0062] an oxime (═NOR′);

[0063] a hydrazone (═N—NR′R′);

[0064] a keto group (═O);

[0065] R2 and R3 can also each represent an —OR″ group in which each ofthe R″ groups represents C₁-C₆, preferably C₁-C₃, alkyl chains whichtogether advantageously form a ring, preferably a 5-membered ring(1,3-dioxolane ring) or a 6-membered ring (1,3-dioxane ring);

[0066] R′ is chosen from a hydrogen atom or a saturated or unsaturated,linear or branched, or cyclic, which can optionally comprise one or moreheteroatoms, C₁-C₁₂, preferably C₁-C₆, alkyl group optionallysubstituted by one or more —OR′′′, —COOR′′′, halogen or —NR′′′R′′′groups; or by an aryl group, preferably a phenyl, optionally substitutedby one or more —OR′′′, —COOR′′′, halogen or —NR′′′R′′′ groups;preferably, R′ represents a hydrogen atom, a methyl, an ethyl, a butyl,a propyl, an isopropyl or a tert-butyl group;

[0067] R′′′ represents a hydrogen atom or a saturated or unsaturated andlinear, branched or cyclic alkyl chain, preferably C₁-C₆ alkyl chain;preferably, R′′′ represents a hydrogen atom, a methyl, an ethyl, abutyl, a propyl, an isopropyl or a tert-butyl group; it being understoodthat, in each of the —NR′R′ and —NR′′′R′′′ groups, the R′ and R′′′substituents respectively are identical or different; with the exceptionof the DHEA derivatives of formula (I) for which:

[0068] R2 and R3 together represent a keto group;

[0069] R4 and R5 together represent a keto group; and

[0070] R1 is as defined above;

[0071] with the exception of the DHEA derivatives of formula (A)

[0072] in which:

[0073] R₁ is chosen from: a hydrogen atom or the following functionalgroups: ester of organic acid comprising 1 to 24 carbon atoms, sulphuricester or phosphoric ester, or carbonaceous ether comprising 1 to 24carbon atoms comprising no or several nitrogen atoms, or ethers ofcarbohydrates comprising 3 to 100 carbon atoms and their derivativescomprising or not comprising one or more nitrogen atoms;

[0074] R₂ is chosen from: a hydrogen atom or an ester functional groupof fatty acid comprising 1 to 24 carbon atoms;

[0075] R₃ is chosen from: a hydrogen atom, an —OH group or groups offormulae: —CO—R₄, —CHOH—R₄, ═CH—CH₃, ═COH—CH₃, —CHR₄—CH₃ or ═O, in whichgroups R₄ is an alkyl group comprising from 1 to 10 carbon atoms whichis or is not substituted.

[0076] The present invention also relates to the optical and/orgeometrical isomers of the DHEA derivatives of formula (I), alone or asa mixture in any proportions, and to the physiologically acceptablesalts of these derivatives, and to their use for improving theappearance of keratinous substances as set forth herein.

[0077] The term “keratinous substances” is understood to mean preferablythe skin, hair fibres (hair and eyelashes) and nails.

[0078] According to a preferred embodiment of the present invention, thepreferred DHEA derivatives of formula (I) are those in which R1represents a saturated or unsaturated, linear or branched, or cyclic,which can comprise one or more heteroatoms, C₁-C₆ alkyl group optionallysubstituted by one or more groups chosen from —OR′ and/or —SR′ and/or—COOR′ and/or —NR′R′ and/or halogen.

[0079] According to another preferred embodiment of the presentinvention, the preferred DHEA derivatives of formula (I) are those inwhich R1 represents an alkylcarbonyl group, the C₁-C₂₀, preferablyC₆-C₁₈, alkyl part of which is saturated or unsaturated and linear,branched or cyclic and optionally substituted by one or more groupschosen from —OR′ and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen.

[0080] When R3 represents a hydrogen atom, R2 is preferably chosen from:

[0081] an —OR6 group in which R6 has the same definitions as those givenabove in a preferred way for R1;

[0082] an amine group —N(R7)₂ in which the R7 substituents, which areidentical or different, have the same definitions as those given abovein a preferred way for R1;

[0083] a thiol group (—SR′);

[0084] a halogen.

[0085] According to another preferred embodiment of the presentinvention, the preferred DHEA derivatives of formula (I) are those inwhich each of the —NR′R′ and/or —NR′′′R′′′ groups represents an aminoacid preferably chosen from L-alanine, L-arginine, L-asparagine,L-aspartic acid, L-cysteine, L-glutamine, L-glutamic acid, glycine,L-hixtidine, L-isoleucine, L-leucine, L-lysine, L-methionine,L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan,L-tyrosine or L-valine.

[0086] Particularly preferred derivatives of formula (I) used accordingto the present invention include the following compounds:

[0087] Androst-5-en-17-one, 3-(acetyloxy)-7-(benzoyloxy)-, (3β,7α);

[0088] Androst-5-en-17-one, 7-hydroxy-3-[[(1-oxopentyl)-sulphonyl]oxy]-,(3β,7β);

[0089] Androst-5-en-17-one, 3-hydroxy-7-(1-oxo-3-phenylpropoxy)-,(3β,7β);

[0090] Androst-5-en-17-one,7-hydroxy-3-[[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propenyl]oxy]-,(3β);

[0091] Androst-5-en-17-one,7-hydroxy-3-[[(9Z)-1-oxo-9-octadecenyl]oxy]-, (3β);

[0092] Pregn-5-en-20-one, 3-(acetyloxy)-7-hydroxy-, (3β,7α);

[0093] Butanoic acid,4-[[[(3β,7Z)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-;

[0094] Butanoic acid,4-[[[(3β,7Z)-3-(acetyloxy)-17-oxoandrost-5-en-7-ylidene]amino]oxy]-,methyl ester;

[0095] Androst-5-en-17-one, 3-(benzoyloxy)-7-(2-methyl-1-oxopropoxy)-,(3β,7β);

[0096] Androst-5-en-17-one, 3-(acetyloxy)-7-fluoro-, (3β,7β);

[0097] Androst-5-en-17-one, 3-(acetyloxy)-7-fluoro-, (3β,7α);

[0098] Acetic acid,[[[(3β,7Z)-3-hydroxy-20-oxopregn-5-en-7-ylidene]amino]oxy]-;

[0099] Acetic acid,[[[(3β,7Z)-3-(acetyloxy)-20-oxopregn-5-en-7-ylidene]amino]oxy]-, methylester;

[0100] Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, (3β);

[0101] Androst-5-en-17-one, 7-bromo-3-hydroxy-, (3β,7α);

[0102] Androst-5-en-17-one, 7-bromo-3-hydroxy-, (3β);

[0103] Pregn-5-en-20-one, 7-bromo-3-hydroxy-, acetate;

[0104] Pregn-5-en-20-one, 3-(acetyloxy)-7-bromo-, (3β);

[0105] Pregn-5-en-20-one, 7α-(-chloro-3β-hydroxy-, acetate;

[0106] Pregn-5-en-20-one, 3-(acetyloxy)-7-bromo-, (3β,7β);

[0107] Pregn-5-en-20-one, 3-(acetyloxy)-7-bromo-, (3β,7α);

[0108] Pregn-5-en-20-one, 7-bromo-3-hydroxy-, benzoate;

[0109] Pregn-5-en-20-one, 7-bromo-3β-hydroxy-, 4-methylvalerate;

[0110] Androst-5-en-17-one, 3β,7α-dihydroxy-, disulphate;

[0111] Acetic acid, [[(3β,7α)-3-hydroxy-17-oxoandrost-5-en-7-yl]thio]-;

[0112] Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 7,17-dioxime, (3β);

[0113] Androst-5-en-17-one, 3-(benzoyloxy)-7-bromo-, (3β,7α);

[0114] Acetic acid,[[[(3β,7Z)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-;

[0115] Acetic acid,[[[(3β,7Z)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-, methylester;

[0116] Acetic acid,[[[3β,7Z)-3-(acetyloxy)-17-oxoandrost-5-en-7-ylidene]amino]oxy]-, methylester;

[0117] Androst-5-en-17-one, 3,7-bis[(trimethylsilyl)-oxy]-, (3β,7β);

[0118] Androst-5-en-17-one,7-hydroxy-3-[[(3-methyl-phenyl)sulphonyl]oxy]-, (3β,7α);

[0119] Androst-5-en-17-one, 3-[(3-chlorobenzoyl)oxy]-7-hydroxy-,(3β,7α);

[0120] Androst-5-en-17-one,7-(3-carboxy-1-oxopropoxy)-3-[(1-oxoheptyl)oxy]-, (3β,7α);

[0121] Pregn-5-en-20-one, 3,7-bis[(trimethylsilyl)oxy]-, (3β,7α);

[0122] Androst-5-en-17-one, 3,7-bis[(trimethylsilyl)-oxy]-, (3β,7α);

[0123] Acetic acid,[[[(3β)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-;

[0124] Androst-5-en-17-one, 3-(acetyloxy)-7-methoxy-, (3β,7α);

[0125] Androst-5-en-17-one, 3-(acetyloxy)-7-methoxy-, (3,7β);

[0126] Pregna-5,16-diene-7,20-dione, 3-(acetyloxy)-, 7,20-dioxime, (3β);

[0127] Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, (3β,7α);

[0128] Pregn-5-en-20-one, 3β,7α-dihydroxy-, 7-(hydrogen sulphate);

[0129] Androst-5-en-17-one, 3-hydroxy-7-(sulphooxy)-, (3β,7α);

[0130] Pregn-5-ene-7,20-dione, 3-hydroxy-,bis[(aminoiminomethyl)hydrazone], (3β);

[0131] Guanidine,1,1′-[(3β-hydroxypregn-5-ene-7,20-diylidene)dinitrilo]di-,dihydrochloride;

[0132] Androst-5-en-17-one, 7-bromo-3β-hydroxy-, benzoate;

[0133] Androst-5-en-17-one, 3-hydroxy-7-methoxy-, (3β,7α);

[0134] Androst-5-en-17-one, 3-hydroxy-7-methoxy-, (3β,7β);

[0135] Androst-5-en-7-one, 3-(acetyloxy)-17-(benzoyloxy)-,7-[O-(phenylmethyl)oxime], (3β,7E,17β);

[0136] Androst-5-ene-3,7,17-triol, 17-(hydrogen sulphate), (3β,7β,17β);

[0137] Androst-5-en-7-one, 3,17-bis(acetyloxy)-,7-[O-(3-hydroxypropyl)oxime], (3β,7Z,17β);

[0138] Propanoic acid,3-[[[(3β,7Z,17β)-3,17-bis(acetyloxy)androst-5-en-7-ylidene]amino]oxy]-,methyl ester;

[0139] Propanoic acid,3-[[[(3β,7Z,17β)-3,17-bis(acetyloxy)androst-5-en-7-ylidene]amino]oxy]-;

[0140] Androst-5-en-17-one,7-(acetyloxy)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, cyclic17-(1,2-ethanediyl acetal), (3β,7β);

[0141] Androst-5-en-7-one,3-(acetyloxy)-17-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, cyclic7-(1,2-ethanediyl acetal), (3β,17β);

[0142] Androst-5-ene-7,17-diol,3-[[(1,1-dimethylethyl)-diphenylsilyl]oxy]-, 17-octanoate, (3β,7β,17β);

[0143] Butanoic acid,4-[[[(3β,7Z,17β)-3-(acetyloxy)-17-hydroxyandrost-5-en-7-ylidene]amino]oxy]-,methyl ester;

[0144] Androst-5-ene-3,7,17-triol, 17-acetate 3-benzoate, (3β,7β,17β);

[0145] Acetic acid,[[[(3β,7Z,17β)-3-(acetyloxy)-17-hydroxyandrost-5-en-7-ylidene]amino]oxy]-,methyl ester;

[0146] Androst-5-ene-3,7,17-triol, 3,17-diacetate 7-methanesulphonate,(3β,17β);

[0147] Androst-5-ene-3,17-diol, 7-bromo-, diacetate, (3β,7β,17β);

[0148] Androst-5-ene-3,7,17-triol, 3-acetate 17-benzoate, (3β,7α,17β);

[0149] Androst-5-ene-3,7,17-triol, 3-acetate 17-benzoate, (3β,7β,17β);

[0150] Androst-5-ene-3,17-diol, 7-bromo-, (3β,7α,17β);

[0151] Androst-5-ene-3,17-diol, 7-bromo-, (3β,17β);

[0152] Androst-5-ene-3,17-diol, 7-bromo-, 3-acetate 17-benzoate,(3β,7α,17β);

[0153] Androst-5-ene-3,17-diol, 7-(phenylsulphinyl)-, diacetate,(3β,17β);

[0154] Androst-5-ene-3,17-diol, 7-(phenylthio)-, diacetate, (3β,17β);

[0155] Androst-5-ene-3,17-diol, 7-bromo-, diacetate, (3β,17β);

[0156] Androst-5-ene-3β,17β-diol, 7-bromo-, dibenzoate;

[0157] Androst-5-ene-3,17-diol, 7-bromo-, 3-acetate 17-benzoate,(3β,7β,17β);

[0158] Propanoic acid,3-[[(3β,7α,17β)-3-(acetyloxy)-17-(benzoyloxy)androst-5-en-7-yl]thio]-,methyl ester;

[0159] Propanoic acid,3-[[(3β,7α,17β)-3,17-dihydroxyandrost-5-en-7-yl]thio]-;

[0160] Androst-5-en-7-one, 3-(acetyloxy)-17-(benzoyloxy)-,7-[O-(phenylmethyl)oxime], (3β,7Z,17β);

[0161] Androst-5-ene-3,7,17-triol, 3-acetate 7,17-dibenzoate,(3β,7α,17β);

[0162] Androst-5-ene-3,7,17-triol, 3-acetate 7,17-dibenzoate,(3β,7β,17β);

[0163] Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, cyclic1,2-ethanediyl acetal, (3β,7β);

[0164] Androst-5-en-7-one, 3-(acetyloxy)-17-(benzoyloxy)-,7-[O-(phenylmethyl)oxime], (3β,17β);

[0165] Androst-5-en-17-one, 3,7-bis(acetyloxy)-, cyclic17-(1,2-ethanediyl acetal), (3β,7α);

[0166] Androst-5-en-17-one, 3-(acetyloxy)-7-hydroxy-, cyclic17-(1,2-ethanediyl acetal), (3β,7β);

[0167] Androst-5-en-17-one, 3-(acetyloxy)-7-hydroxy-, cyclic17-(1,2-ethanediyl acetal), (3β,7α);

[0168] Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 7,17-dioxime, (3β);

[0169] Androst-5-en-3-ol, 7-bromo-, benzoate, (3β);

[0170] Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 17-(1,2-ethanediylacetal), 7-oxime, (3β,7Z);

[0171] Acetic acid,[[[(3β,7Z)-3-(acetyloxy)-17,17-[1,2-ethanediylbis(oxy)]androst-5-en-7-ylidene]amino]-oxy]-,methyl ester;

[0172] Androst-5-en-7-one, 3,17-bis[(trimethylsilyl)-oxy]-,O-methyloxime, (3β,17β);

[0173] Androst-5-en-7-one, 3,17-dihydroxy-, oxime, (3β,17β);

[0174] Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 17-oxime, (3β);

[0175] Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 7,17-dioxime, (3β);

[0176] Acetic acid,[[[(3β,17β)-3,17-dihydroxyandrost-5-en-7-ylidene]amino]oxy]-;

[0177] Acetic acid,[[[(3β)-17,17-[1,2-ethanediylbis-(oxy)]-3-hydroxyandrost-5-en-7-ylidene]amino]-oxy]-;

[0178] Silane,[[(3β,7α,17β)-androst-5-ene-3,7,17-triyl]tris(oxy)]tris[trimethyl]-;

[0179] Benzenesulphonic acid, 4-methyl-,[(3β,17β)-3,17-bis(acetyloxy)androst-5-en-7-ylidene]hydrazide;

[0180] Androst-5-en-7-one, 3,17-bis(acetyloxy)-, oxime, (3β,17β);

[0181] Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, cyclic1,2-ethanediyl acetal, (3β,7α);

[0182] Androst-5-en-17-one, 7-bromo-3-hydroxy-, cyclic 1,2-ethanediylacetal, (3β,17α);

[0183] Androst-5-en-3β-ol, 7α-bromo-, acetate;

[0184] Androst-5-en-3β-ol, 7α-bromo-.

[0185] The DHEA derivatives of formula (I) according to the inventionare readily accessible from a synthetic viewpoint, in particular by theuse of one of the synthetic methods disclosed in Patents U.S. Pat. No.5,424,463, FR-2 771 105, U.S. Pat. Nos. 5,869,709, 6,111,118, WO94/085888 and WO 01/23405 and/or in the document Tetrahedron Letters,1997, 38, 119-122, the disclosure of which is hereby incorporated byreference in their entirety.

[0186] More particularly, the present invention relates to the use,preferably the cosmetic use, of at least one DHEA derivative of formula(I) as defined above for preventing or treating cutaneous signs ofageing and/or a faded complexion and/or disorders of pigmentation of theskin or hair and/or drying of the skin and/or hyperseborrhoea and/orimperfections related to hyperseborrhoea and/or sensitive skin and/ordandruff and/or hair loss and/or canities.

[0187] The term “cutaneous signs of ageing” is understood to include atleast wrinkles and fine lines, loss of firmness and/or of elasticity ofthe skin, cutaneous atrophy, a more uneven skin grain with presence ofdilated pores, loss of radiance of the skin and/or pigmentary blemishes.

[0188] The term “sensitive skin” is understood to mean skin which hasbeen characterized in Patent EP 0 680 749 B1, hereby incorporated byreference in its entirety, which shows that the symptoms related tosensitive skin consisted of more or less painful sensations experiencedin a cutaneous region, such as smarting, pins and needles, itching orpruritus, burning sensations, redness, warming sensations, discomfort,stabbing pains, and the like. These symptoms may be displayed inresponse to various factors, such as, inter alia, sweat, friction, theemotions, foods, the wind, shaving, soap, surfactants, hard water with ahigh calcium concentration, temperature variations or wool.

[0189] According to another aspect of the present invention, acomposition including, in a physiologically acceptable medium, at leastone DHEA derivative of formula (I) as defined above and at least onecompound chosen from: a desquamating agent, a moisturizing agent, adepigmenting or propigmenting agent, an antiglycation agent, anNO-synthase inhibitor, a 5α-reductase inhibitor, a lysyl and/or prolylhydroxylase inhibitor, an agent which stimulates the synthesis of dermalor epidermal macromolecules and/or which prevents their decomposition,an agent which stimulates the proliferation of fibroblasts andkeratinocytes and/or the differentiation of keratinocytes, a musclerelaxant, a compound which reduces irritation of neurogenic origin, anantimicrobial agent, a tightening agent, an agent for combatingpollution or free radicals, or a soothing agent capable of inhibiting atleast one enzyme chosen from phospholipases A2, lipoxygenases and/orhuman prostaglandin synthetases is provided.

[0190] The present invention also relates to a composition including, ina physiologically acceptable medium, at least one DHEA derivative offormula (I) as defined above and at least one UV screening agent chosenfrom UV-A and/or UV-B screening agents and/or at least one optionallycoated inorganic pigment.

[0191] The term “physiologically acceptable medium” is understood tomean a medium compatible with the skin and/or its superficial growths.

[0192] According to preferred embodiments, the composition according tothe present invention preferably includes from 0.00001% to 10% by weightof DHEA derivative of formula (I) as defined above with respect to thetotal weight of the composition. More preferably, this compositionincludes from 0.001% to 5% by weight of DHEA derivative of formula (I)as defined above with respect to the total weight of the composition.

[0193] Examples of the various compounds capable of being introducedinto the composition according to the invention will now be described.

[0194] 1. Desquamating and Moisturizing Agents

[0195] The term “desquamating agent” is understood to mean any compoundcapable of acting:

[0196] either directly on desquamation by promoting exfoliation, such asβ-hydroxy acids, in particular salicylic acid and its derivatives(including 5-(n-octanoyl)salicylic acid); α-hydroxy acids, such asglycolic acid, citric acid, lactic acid, tartaric acid, malic acid ormandelic acid; urea; gentisic acid; oligofucoses; cinnamic acid; Saphorajaponica extract; hydroxystilbenes, including in particular resveratrol;

[0197] or on the enzymes involved in desquamation or decomposition ofthe corneodesmosomes, such as glycosidases, stratum corneum chymotrypticenzyme (SCCE) or other proteases (for example, trypsin,chymotrypsin-like). Suitable agents also include, for example, agentswhich chelate inorganic salts: EDTA;N-acyl-N,N′,N′-ethylenediaminetriacetic acid; aminosulphonic compoundsand in particular N-(2-hydroxyethyl)piperazine-N′-2-ethanesulphonic acid(HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine) derivatives;derivatives of α-amino acids of glycine type (as disclosed in EP-0 852949); honey; or sugar derivatives, such as O-octanoyl-6-D-maltose andN-acetylglucosamine.

[0198] The term “moisturizing agent” is understood to mean:

[0199] either a compound which acts on the barrier function, for thepurpose of keeping the stratum corneum moisturized, or an occlusivecompound. Examples of such agents include ceramides, sphingoid-basedcompounds, lecithins, glycosphingolipids, phospholipids, cholesterol andits derivatives, phytosterols (stigmasterol, β-sitosterol orcampesterol), essential fatty acids, 1,2-diacylglycerol, 4-chromanone,pentacyclic triterpenes, petroleum jelly and lanolin;

[0200] or a compound which directly increases the water content of thestratum corneum, such as threalose and its derivatives, hyaluronic acidand its derivatives, glycerol, pentanediol, pidolates, serine, xylitol,sodium lactate, glyceryl polyacrylate, ectoin and its derivatives,chitosan, oligo- and polysaccharides, cyclic carbonates,N-lauroylpyrrolidonecarboxylic acid and N-a-benzoyl-L-arginine;

[0201] or a compound which activates the sebaceous glands, such assteroid derivatives (including DHEA) and vitamin D and its derivatives.

[0202] These compounds preferably represent from 0.001% to 30%, morepreferably from 0.01 to 20%, of the total weight of the compositionaccording to the present invention.

[0203] The composition according to the present invention comprising theabove-mentioned desquamating and moisturizing agents is preferablyintended for the prevention or the treatment of drying of the skin andin particular of xerosis.

[0204] 2. Depigmenting or Propigmenting Agents

[0205] The depigmenting agents capable of being incorporated in thecomposition according to the present invention comprise, for example,the following compounds: kojic acid; ellagic acid, arbutin and itsderivatives, such as those disclosed in EP-895 779 and EP-524 109;hydroquinone; aminophenol derivatives such as those disclosed in PCTpatent applications WO 99/10318 and WO 99/32077, in particularN-cholesteryloxycarbonyl-para-aminophenol andN-ethyloxycarbonyl-para-aminophenol; iminophenol derivatives, inparticular those disclosed in PCT patent application WO 99/22707;L-2-oxothiazolidine-4-carboxylic acid or procysteine, and its salts andesters; ascorbic acid and its derivatives, in particular ascorbylglucoside; and plant extracts, in particular of liquorice, of blackberryand of skull cap, without this list being limiting.

[0206] Examples of suitable propigmenting agents include the extracts ofburnet (Sanguisorba officinalis) sold by Maruzen, and extracts ofchrysanthemum (Chrysanthemum morifolium).

[0207] The composition according to the present invention comprising theabovementioned depigmenting agents is preferably intended for theprevention or the treatment of hyperpigmentation, in particular ofpigmentary blemishes related to ageing of the skin.

[0208] The composition including the above-mentioned propigmentingagents is preferably intended for the treatment of canities.

[0209] 3. Antiglycation Agent

[0210] The term “antiglycation agent” is understood to mean a compoundwhich prevents and/or reduces the glycation of skin proteins, inparticular of dermal proteins, such as collagen.

[0211] Examples of suitable antiglycation agents include plant extractsof the Ericaceae family, such as an extract of blueberry (Vacciniumangustifolium); ergothioneine and its derivatives; and hydroxystilbenesand their derivatives, such as resveratrol and3,3′,5,5′-tetrahydroxystilbene. Suitable antiglycation agents of thistype are disclosed in Applications FR 99/16166, FR 00/08158, FR 99/09267and FR 99/16168, respectively. Resveratrol is particularly preferred foruse in this invention.

[0212] The composition according to the invention comprising anantiglycation agent as defined above is preferably used to prevent ortreat signs of cutaneous ageing, in particular to prevent or treat lossof tonicity and/or of elasticity of the skin.

[0213] 4. NO-Synthase Inhibitor

[0214] Examples of NO-synthase inhibitors suitable for use in thepresent invention include a plant extract of the species Vitis viniferawhich is sold in particular by Euromed under the name Leucocyanidines deraisins extra, or by Indena under the name Leucoselect®, or, finally, byHansen under the name Extrait de marc de raisin; a plant extract of thespecies Olea europaea which is preferably obtained from olive treeleaves and which is sold in particular by Vinyals in the dry extractform or by Biologia & Technologia under the trade name Eurol BT; and aplant extract of the species Gingko biloba which is preferably a dryaqueous extract of this plant sold by Beaufour under the trade nameGinkgo biloba extrait standard.

[0215] The composition according to the invention comprising anNO-synthase inhibitor as defined above is preferably used to prevent ortreat signs of cutaneous ageing and/or sensitive skin.

[0216] 5. 5α-Reductase Inhibitor

[0217] When the composition according to the invention comprises a5α-reductase inhibitor, suitable such inhibitors include, for example,

[0218] retinoids and in particular retinol;

[0219] sulphur and sulphur derivatives;

[0220] zinc salts, such as zinc lactate, gluconate, pidolate,carboxylate, salicylate and/or cysteate;

[0221] selenium chloride;

[0222] vitamin B6 or pyridoxine;

[0223] the mixture of capryloyl glycine, of sarcosine and of extract ofCinnamomum zeylanicum sold in particular by Seppic under the trade nameSepicontrol A5®;

[0224] an extract of Laminaria saccharina, sold in particular by Secmaunder the trade name Phlorogine®;

[0225] an extract of Spiraea ulmaria, sold in particular by Silab underthe trade name Sebonormine®;

[0226] plant extracts of the species Arnica montana, Cinchonasuccirubra, Eugenia caryophyllata, Humulus lupulus, Hypericumperforatum, Mentha piperita, Rosmarinus officinalis, Salvia officinalisand Thymus vulgaris, all sold, for example, by Maruzen;

[0227] an extract of Serenoa repens sold in particular by Euromed;

[0228] plant extracts of the genus Silybum;

[0229] plant extracts comprising sapogenins and in particular extractsof Dioscorea species rich in diosgenin or hecogenin; and

[0230] extracts of Eugenia caryophyllata comprising eugenol or eugenylglucoside.

[0231] The 5α-reductase inhibitor preferably is present from 0.001% to10%, more preferably from 0.01 to 5%, of the total weight of thecomposition according to the present invention. When the compositionincludes such a compound, it is particularly well suited to preventingor treating seborrhoea and/or hirsutism and/or androgen-dependentalopecia.

[0232] 6. Lysyl and/or Prolyl Hydroxylase Inhibitor

[0233] Preferred examples of lysyl and/or prolyl hydroxylase inhibitorswhich can be used in the composition according to the present inventioninclude 2,4-diaminopyrimidine 3-oxide or 2,4-DPO, disclosed in PCTpatent application WO 96/09048, and 2,4-diamino-6-piperidinopyrimidine3-oxide or “Minoxidil”, disclosed in Patents U.S. Pat. Nos. 4,139,619and 4,596,812.

[0234] Preferably, these compounds are present in the compositionaccording to the present invention at a level of 0.001 to 5% by weight,more preferably at a level of 0.01 to 5% by weight, with respect to thetotal weight of the composition.

[0235] The composition including the lysyl and/or prolyl hydroxylaseinhibitor and the DHEA derivative of formula (I) according to theinvention is preferably used in the treatment of alopecia.

[0236] 7. Agent Which Stimulates the Synthesis of Dermal or EpidermalMacromolecules and/or Which Prevents Their Decomposition

[0237] Suitable active principles which stimulate dermal macromoleculesinclude, for example, those which act:

[0238] either on the synthesis of collagen, such as extracts of Centellaasiatica; asiaticosides and derivatives; ascorbic acid or vitamin C andits derivatives, synthetic peptides, such as iamine, biopeptide CL orthe palmitoyloligopeptide sold by Sederma; peptides extracted fromplants, such as the soybean hydrolysate sold by Coletica under the tradename Phytokine®; or plant hormones, such as auxins and cinnamic acid andits derivatives, as disclosed in the European patent applicationpublished under the number 0 925 779;

[0239] or on the synthesis of elastin, such as the extract ofSaccharomyces cerevisiae sold by LSN under the trade name Cytovitin®;and the extract of the alga Macrocystis pyrifera sold by Secma under thetrade name Kelpadelie®;

[0240] or on the synthesis of glycosaminoglycans, such as the product offermentation of milk by Lactobacillus vulgaris sold by Brooks under thetrade name Biomin yogourth®; the extract of the brown alga Padinapavonica sold by Alban Müller under the trade name HSP3®; and theextract of Saccharomyces cerevisiae available in particular from Silabunder the trade name Firmalift® or from LSN under the trade nameCytovitin®;

[0241] or on the synthesis of fibronectin, such as the extract of Salinazooplankton sold by Seporga under the trade name GP4G®; the yeastextract available in particular from Alban Müller under the trade nameDrieline®; and the palmitoyl pentapeptide sold by Sederma under thetrade name Matrixil®;

[0242] or on the inhibition of metalloproteinases (MMP), such as moreparticularly MMP 1, 2, 3 or 9. Suitable examples of such compoundsinclude retinoids and derivatives; isoflavonoids; oligopeptides andlipopeptides, lipoamino acids; the malt extract sold by Coletica underthe trade name Collalift®; extracts of blueberry or of rosemary;carotenoids, including in particular lycopene; or isoflavones, theirderivatives or the plant extracts comprising them, in particularextracts of soybean (sold, for example, by Ichimaru Pharcos under thetrade name Flavosterone SB®), of red clover, of flax, of kakkon or ofsage (as disclosed in the French Patent Application Number 00 10203);

[0243] or on the inhibition of serine proteases, such as leukocyteelastase or cathepsin G. Suitable examples of such compounds include thepeptide extract of Leguminosae (Pisum sativum) seeds sold by LSN underthe trade name Parelastyl®; and heparinoids and pseudodipeptides.

[0244] Preferred active principles which stimulate epidermalmacromolecules include, for example, filaggrin and keratins, of theextract of lupin sold by Silab under the trade name Structurine®; theextract of beech Fagus sylvatica buds sold by Gattefossé under the tradename Gatuline®; and the extract of Salina zooplankton sold by Seporgaunder the trade name GP4G®.

[0245] The composition according to the present invention including oneor more of the above compounds is particularly well suited to use in theprevention or the treatment of cutaneous signs of ageing, in particularof loss of firmness and/or of elasticity of the skin.

[0246] 8. Agent Which Stimulates the Proliferation of Fibroblasts orKeratinocytes and/or the Differentiation of Keratinocytes

[0247] Examples of agents which stimulate the proliferation offibroblasts which can be used in the composition according to thepresent invention include plant proteins or polypeptides, extracts, inparticular of soybean (for example, a soybean extract sold by LSN underthe name Eleseryl SH-VEG 8® or sold by Silab under the trade nameRaffermine®); and plant hormones, such as gibberellins and cytokinins.

[0248] Examples of agents which stimulate the proliferation ofkeratinocytes which can be used in the composition according to thepresent invention include retinoids, such as retinol and its esters,including retinyl palmitate; the extracts of walnut meal sold byGattefossé; and the extracts of Solanum tuberosum sold by Sederma.

[0249] Example of agents which stimulate the differentiation ofkeratinocytes include inorganic materials, such as calcium; the extractof lupin sold by Silab under the trade name Photopreventine®; sodiumβ-sitosteryl sulphate, sold by Seporga under the trade namePhytocohésine®; and the extract of maize sold by Solabia under the tradename Phytovityl®.

[0250] The composition according to the present invention comprisingthese compounds is preferably intended to be used to prevent or treatcutaneous signs of ageing.

[0251] 9. Muscle Relaxant

[0252] Examples of muscle relaxants which can be used in the compositionaccording to the present invention include calcium inhibitors, such asalverine and its salts, chloride-channel openers, such as diazepam, andinhibitors of catecholamines and of acetylcholine, such as thehexapeptide argireline R sold by Ilipotec.

[0253] The composition according to the present invention comprisingthese compounds is preferably intended to be used to prevent or treatcutaneous signs of ageing and in particular wrinkles.

[0254] 10. Antimicrobial Agent

[0255] Examples of antimicrobial agents capable of being used in thecomposition according to the present invention include2,4,4′-trichloro-2′-hydroxydiphenyl ether (or triclosan),3,4,4′-trichlorocarbanilide, phenoxyethanol, phenoxypropanol,phenoxyisopropanol, hexamidine isethionate, metronidazole and its salts,miconazole and its salts, itraconazole, terconazole, econazole,ketoconazole, saperconazole, fluconazole, clotrimazole, butoconazole,oxiconazole, sulfaconazole, sulconazole, terbinafin, ciclopirox,ciclopiroxolamine, undecylenic acid and its salts, benzoyl peroxide,3-hydroxybenzoic acid, 4-hydroxybenzoic acid, phytic acid,N-acetyl-L-cysteine, lipoic acid, azelaic acid and its salts,arachidonic acid, resorcinol, 2,4,4′-trichloro-2′-hydroxydiphenyl ether,3,4,4′-trichlorocarbanalide, octopirox, octoxyglycerin, octanoylglycine,caprylyl glycol, 10-hydroxy-2-decanoic acid, dichlorophenylimidazoledioxolane and its derivatives disclosed in Patent WO 93/18743, farnesol,phytosphingosines and their mixtures.

[0256] The preferred antimicrobial agents are triclosan, phenoxyethanol,octoxyglycerin octanoylglycine, 10-hydroxy-2-decanoic acid, caprylylglycol, farnesol and azelaic acid.

[0257] Preferably, the antimicrobial agent can be used in thecomposition according to the present invention in an amount representingfrom 0.1 to 20%, more preferably from 0.1 to 10%, of the total weight ofthe composition.

[0258] The composition including the DHEA derivative of formula (I) andthe antimicrobial agent is particularly well suited to use in thetreatment of greasy skin with a tendency towards acne, acne or dandruffof the scalp.

[0259] 11. Tightening Agent

[0260] The term “tightening agent” is understood to mean a compoundcapable of exerting tension on the skin, the effect of which is totemporarily render less dinstinct unevennesses in the surface of theskin, such as wrinkles and fine lines.

[0261] Examples of suitable tightening agents which can be used in thecomposition according to the present invention include:

[0262] (1) polyurethane latices or acrylic-silicone latices, inparticular those disclosed in Patent Application EP-1 038 519, such as apolydimethylsiloxane grafted with propylthio[poly(methyl acrylate)],propylthio-[poly(methyl methacrylate)] and propylthio[poly-(methacrylicacid)] or a polydimethylsiloxane grafted with propylthio[poly(isobutylmethacrylate)] and propylthio[poly(methacrylic acid)]. Such graftedsilicone polymers are sold, for example, by 3M under the trade names VS80, VS 70 or LO21.

[0263] (2) soybean or wheat plant proteins, and/or

[0264] (3) sodium magnesium silicates (Laponites).

[0265] The compositions according to the present invention comprisingthe above tightening agents are advantageously intended for thetreatment of cutaneous signs of ageing, in particular of wrinkles andfine lines.

[0266] 12. Agent for Combating Pollution or Free Radicals

[0267] The expression “agent for combating pollution” is understood tomean any compound capable of trapping ozone, mono- or polycyclicaromatic compounds, such as benzopyrene, and/or heavy metals, such ascobalt, mercury, cadmium and/or nickel. The term “agent for combatingfree radicals” is understood to mean any compound capable of trappingfree radicals.

[0268] Suitable examples of ozone-trapping agents which can be used inthe composition according to the present invention include vitamin C andits derivatives, including ascorbyl glucoside; phenols and polyphenols,in particular tannins, ellagic acid and tannic acid; epigallocatechinand the natural extracts comprising it; extracts of olive tree leaf;extracts of tea, in particular of green tea; anthocyans; extracts ofrosemary; phenol acids, in particular chlorogenic acid; stilbenes, inparticular resveratrol; sulphur-comprising amino acid derivatives, inparticular S-carboxymethylcysteine; ergothioneine; N-acetyl-cysteine;chelating agents, such asN,N′-bis(3,4,5-trimethoxybenzyl)ethylenediamine or one of its salts,metal complexes or esters; carotenoids, such as crocetin; and variousstarting materials, such as the mixture of arginine, histidineribonucleate, mannitol, adenosine triphosphate, pyridoxine,phenylalanine, tyrosine and hydrolysed RNA sold by LaboratoiresSerobiologiques under the trade name CPP LS 2633-12F®, the water-solublefraction of maize sold by Solabia under the trade name Phytovityl®, themixture of extract of fumitory and extract of lemon sold under the nameUnicotrozon C-49® by Induchem, and the mixture of extracts of ginseng,of apple, of peach, of wheat and of barley sold by Provital under thetrade name Pronalen Bioprotect®.

[0269] Suitable examples of agents which trap mono- or polycyclicaromatic compounds which can be used in the composition according to thepresent invention include tannins, such as ellagic acid; indolederivatives, in particular indole-3-carbinol; extracts of tea, inparticular of green tea; extracts of water hyacinth or Eichhorniacrassipes; and the water-soluble fraction of maize sold by Solabia underthe trade name Phytovityl®.

[0270] Finally, suitable examples of agents which trap heavy metalswhich can be used in the composition according to the present inventioninclude chelating agents, such as EDTA, the pentasodium salt ofethylenediaminetetramethylenephosphonic acid, andN,N′-bis(3,4,5-trimethoxybenzyl)ethylenediamine or one of its salts,metal complexes or esters; phytic acid; chitosan derivatives; extractsof tea; in particular of green tea; tannins, such as ellagic acid;sulphur-comprising amino acids, such as cysteine; extracts of waterhyacinth (Eichhornia crassipes) and the water-soluble fraction of maizesold by Solabia under the trade name Phytovityl®.

[0271] The agents for combating free radicals which can be used in thecomposition according to the present invention can also comprise, inaddition to some agents for combating pollution mentioned above, vitaminE and its derivatives, such as tocopheryl acetate; bioflavonoids;coenzyme Q10 or ubiquinone; certain enzymes, such as catalase,superoxide dismutase, lactoperoxidase, glutathione peroxidase and quionereductases; glutathione, benzylidenecamphor; benzylcyclanones;substituted naphthalenones; pidolates; phytanthriol; γ-oryzanol;lignans; and melatonin.

[0272] The compositions according to the present invention comprisingthe above agents for combating pollution and/or for combating freeradicals are preferably intended for the prevention or the treatment ofcutaneous signs of ageing, in particular of wrinkles and of loss offirmness and of elasticity of the skin and of dehydration. Also, theycan be intended for the prevention or the treatment of a fadedcomplexion.

[0273] 13. UVA and/or UVB Screening Agent and Optionally CoatedInorganic Pigments

[0274] The composition according to the present invention can includeone or more UV screening agents capable of screening out UVA and/or UVBradiation.

[0275] Suitable examples of compounds capable of screening out UVAradiation include:

[0276] (1) benzophenone derivatives, for example:

[0277] 2,4-dihydroxybenzophenone (benzophenone-1);

[0278] 2,2′,4,4′-tetrahydroxybenzophenone (benzophenone-2);

[0279] 2-hydroxy-4-methoxybenzophenone (benzophenone-3), available fromBASF under the trade name Uvinul M40;

[0280] 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid (benzophenone-4)and its sulphonate form (benzophenone-5), available from BASF under thetrade name Uvinul MS40;

[0281] 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (benzophenone-6);

[0282] 5-chloro-2-hydroxybenzophenone (benzophenone-7);

[0283] 2,2′-dihydroxy-4-methoxybenzophenone (benzophenone-8);

[0284] the disodium salt of2,2′-dihydroxy-4,4′-dimethoxybenzophenone-5,5′-disulphonic diacid(benzophenone-9);

[0285] 2-hydroxy-4-methoxy-4′-methylbenzophenone (benzophenone-10);

[0286] benzophenone-11;

[0287] 2-hydroxy-4-(octyloxy)benzophenone (benzophenone-12);

[0288] benzophenone-3 and benzophenone-5 being preferred;

[0289] (2) triazine derivatives and in particular2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine,available from Ciba-Geigy under the trade name Tinosorb S and2,2′-methylenebis[6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol],available from Ciba-Geigy under the trade name Tinosorb M;

[0290] (3) benzene-1,4-di(3-methylidenecamphor-10-sulphonic acid),optionally in the partially or completely neutralized form, and

[0291] (4) their mixtures.

[0292] Suitable examples of compounds capable of filtering out UVBradiation include:

[0293] (1) salicylic acid derivatives, in particular homomenthylsalicylate and octyl salicylate;

[0294] (2) cinnamic acid derivatives, in particular 2-ethyl-hexyl2-methoxycinnamate, available from Givaudan under the trade name ParsolMCX;

[0295] (3) liquid β,β-diphenylacrylate derivatives, in particular2-ethylhexyl α-cyano-α,β-diphenylacrylate, or octocrylene, availablefrom BASF under the trade name Uvinul N539;

[0296] (4) p-aminobenzoic acid derivatives;

[0297] (5) 4-methylbenzylidenecamphor, available from Merck under thetrade name Eusolex 6300;

[0298] (6) 2-phenylbenzimidazole-5-sulphonic acid, sold under the tradename “Eusolex 232” by Merck;

[0299] (7) 1,3,5-triazine derivatives, in particular:

[0300]2,4,6-tris[p-(2′-ethylhexyl-1′-oxycarbonyl)-anilino]-1,3,5-triazine,available from BASF under the trade name Uvinul T150, and

[0301] the compound corresponding to the following formula (A):

[0302] in which R′ denotes a 2-ethylhexyl radical and R denotes atert-butyl radical, available from Sigma 3V under the trade name UvasorbHEB;

[0303] (8) their mixtures.

[0304] Suitable examples of compound capable of screening out UVA andUVB radiation include: (1) plant extracts, in particular of rosemary(rosmaric acid) and of the Leontopodium genus, in particular a plantspecies chosen from Leontopodium alpinum or Leontopodium stracheyi;

[0305] (2) the benzotriazole silicone corresponding to the followinggeneral formula (B):

[0306] This benzotriazole silicone and its method of preparation aredisclosed in particular in Application FR-A-2 642 968.

[0307] Suitable examples of optionally coated inorganic pigments includenanopigments comprising titanium oxide, iron oxide, zinc oxide,zirconium oxide or cerium oxide which are optionally coated with aluminaand/or aluminium stearate.

[0308] 14. Compounds Which Reduce Irritation of Neurogenic Origin

[0309] Suitable examples of compounds which reduce irritation ofneurogenic origin include:

[0310] substance P antagonists and in particular those mentioned inPatent EP 0 680 749, extracts of at least one non-photosyntheticfilamentous bacterium, particularly of the strains of Vitreoscillafiliformis disclosed in Patent EP 0 761 204, the thermal watersdisclosed in Patent EP 0 764 440, extracts of at least one plant of thefamily of the Rosaceae, particularly of the species Rosa gallica,disclosed in the European Patent Application published under the numberNo. 0 906 752, and the alkaline earth metals disclosed in the EuropeanPatent Applications published under the numbers 0 737 471 and 0 770 392;

[0311] CGRP antagonists, in particular those mentioned in Patent EP 0765 668 and in particular extracts of members of the Iridaceae family,particularly of the species Iris pallida;

[0312] NO-synthase inhibitors;

[0313] bradykinin antagonists and in particular those mentioned in theEuropean Patent Application published under the number 0 909 556;

[0314] cytokine antagonists;

[0315] histamine antagonists;

[0316] antagonists of interleukin 1 and/or of tumour necrosis factor α(TNF-α) and in particular those mentioned in the European PatentApplications published under the numbers 0 892 642 and 0 764 444,particularly the peptide Modulene, the tripeptide Lysine-Proline-Valine(KPV) and an extract of at least one plant of the family of the Labitae,particularly of the species Rosmarinus officinalis;

[0317] sodium-channel blockers chosen in particular from: amiloride,quinidine, quinidine sulphate, apamine, cyproheptadine, loperamide andN-acetylprocainamide;

[0318] potassium-channel openers and in particular minoxidil and itsderivatives.

[0319] 15. Soothing Agents Capable of Inhibiting at Least One Enzyme

[0320] Examples of suitable soothing agents capable of inhibiting atleast one enzyme chosen from phospholipases A2, lipoxygenases and/orhuman prostaglandin synthetases include:

[0321] pentacyclic triterpenes and plant extracts (in particular ofGlycyrrhiza glabra) comprising, especially oleanolic acid and its salts,β-glycyrrhetinic acid and its salts and/or its derivatives, such asglycyrrhetic acid monoglucuronide, stearyl glycyrrhetinate or3-stearoyloxyglycyrrhetic acid;

[0322] betulinic acid and its salts;

[0323] extracts of Paeonia suffruticosa;

[0324] extracts of Paeonia lactiflora;

[0325] calophyllum oil;

[0326] phycosaccharides, in particular Hydrolysed Algin® or HydrolysedAlgin and Zinc Sulfate® from Codif;

[0327] canola oil;

[0328] tamanu oil;

[0329] α-bisabolol;

[0330] extracts of camomile;

[0331] allantoin;

[0332] the phosphoric diester of vitamin E and C, in particularSepivital EPC® from Seppic;

[0333] omega-3 unsaturated oils, such as musk rose oils, blackcurrantseed oils, echium oils or fish oils;

[0334] extracts of plankton, in particular Omega planctone from Secma;

[0335] the combination of sodium palmitoylproline and of Nymphaea alba,in particular Seppicalm VG® from Seppic;

[0336] extracts of Pygeum;

[0337] extracts of Boswellia serrata, in particular Soothex® from Quest;

[0338] extracts of Centipeda cunnighamii, in particular Phytoplenolin®from BioBotanica;

[0339] extracts of Helianthus annuus, in particular Helioxine® fromSilab;

[0340] extracts of Linum usitatissimum, in particular Sensiline® fromSilab;

[0341] tocotrienols;

[0342] extracts of Cola nitida;

[0343] piperonal;

[0344] extracts of clove;

[0345] extracts of rosebay willow-herb (Epilobium angustifolium);

[0346] extracts of Aloe vera;

[0347] cortisone;

[0348] hydrocortisone;

[0349] indomethacin;

[0350] betamethasone.

[0351] In addition to the compound or compounds described above, thecomposition according to the present invention generally includes aneffective amount of DHEA derivatives of formula (I) as defined above,which is sufficient to produce the desired effect. It thus comprises,for example, from 0.00001% to 10% by weight of the DHEA derivative offormula (I) with respect to the total weight of the composition,preferably from 0.001% to 5% by weight of the DHEA derivative of formula(I) with respect to the total weight of the composition, and morepreferably from 0.1 to 0.5% by weight of the DHEA derivative of formula(I) with respect to the total weight of the composition.

[0352] The compositions according to the present invention may beintended for a cosmetic or pharmaceutical application, particularly adermatological application. Preferably, the compositions according tothe present invention are intended for a cosmetic application.

[0353] The compositions according to the present invention can be usedfor cosmetic purposes, for improving the appearance of keratinoussubstances, in particular for preventing or treating cutaneous signs ofageing and/or a faded complexion and/or disorders of pigmentation of theskin or of the hair and/or drying of the skin and/or hyperseborrhoeaand/or imperfections related to hyperseborrhoea and/or sensitive skinand/or dandruff and/or hair loss and/or canities.

[0354] The compositions according to the invention are preferablysuitable for topical application to keratinous substances, such as theskin, hair, eyelashes or nails. They can be provided in anypharmaceutical dosage form normally used for this type of application,for example, in the form of an aqueous or oily solution, or anoil-in-water or water-in-oil emulsion, of a silicone emulsion, of amicroemulsion or nanoemulsion, of an aqueous or oily gel or of a liquid,pasty or solid anhydrous product.

[0355] These compositions can be more or less fluid and have theappearance of a white or coloured cream, of an ointment, of a milk, of alotion, of a serum, of a paste, of a foam or of a gel. They can also beapplied to the skin in the form of an aerosol, patch or powder. They canalso be provided in the solid form, for example in the form of a stick.They can be used as product for caring for and/or as product for makingup the skin. Also, they can be provided in the form of a shampoo orconditioner.

[0356] The composition of the present invention can also comprise theadjuvants which are standard in the cosmetics field, such as, forexample, hydrophilic or lipophilic gelling agents, preservatives,antioxidants, solvents, fragrances, fillers, pigments, odour absorbersand colouring materials. The amounts of these various adjuvants arethose conventionally used in the field under consideration, for example,from 0.01 to 20% of the total weight of the composition. Theseadjuvants, depending on their nature, can be introduced into the fattyphase or into the aqueous phase. These adjuvants, and theirconcentrations, must be such that they do not harm the advantageousproperties of the DHEA derivative of formula (I) according to thepresent invention.

[0357] When the composition according to the invention is an emulsion,the proportion of the fatty phase preferably ranges from 2 to 80% byweight, more preferably from 5 to 50%, by weight with respect to thetotal weight of the composition. The fatty substances, the emulsifiersand the coemulsifiers used in the composition in the form of an emulsionare chosen from those conventionally used in the field underconsideration. The emulsifier and the coemulsifier are preferablypresent in the composition in a proportion ranging from 0.3 to 30% byweight, more preferably from 0.5 to 20% by weight, with respect to thetotal weight of the composition.

[0358] Examples of suitable fatty substances which can be used in theinvention include oils and in particular mineral oils (liquidpetrolatum), oils of vegetable origin (avocado oil, soybean oil), oilsof animal origin (lanolin oil), synthetic oils (perhydro-squalene),silicone oils (cyclomethicone) and fluorinated oils(perfluoropolyethers). Use may also be made, as fatty substances, offatty alcohols, such as cetyl alcohol, of fatty acids, of waxes and ofgums and in particular silicone gums.

[0359] Examples of suitable emulsifiers and coemulsifiers which can beused in the invention include, for example, esters of fatty acid and ofpolyethylene glycol, such as PEG-100 stearate, PEG-50 stearate andPEG-40 stearate; esters of fatty acid and of polyol, such as glycerylstearate, sorbitan tristearate and oxyethylenated sorbitan stearatesavailable under the trade names Tween® 20 or Tween® 60, for example; andtheir mixtures.

[0360] Suitable examples of hydrophilic gelling agents includecarboxyvinyl polymers (carbomer), acrylic copolymers, such asacrylate/alkyl acrylate copolymers, polyacrylamides, polysaccharides,clays and natural gums. Suitable examples of lipophilic gelling agentsinclude modified clays, such as bentones, metal salts of fatty acids andhydrophobic silica.

[0361] The present invention also relates to a process for the cosmetictreatment of keratinous substances comprising the topical application tothe keratinous substances of a composition including, in aphysiologically acceptable medium, at least one DHEA derivative offormula (I) as defined above, alone or in combination with at least onecompound as described above.

[0362] The present invention also relates to a process for the cosmetictreatment of cutaneous signs of ageing and/or a faded complexion and/ordisorders of pigmentation of the skin or of the hair and/or drying ofthe skin and/or hyperseborrhoea and/or imperfections related tohyperseborrhoea and/or sensitive skin and/or dandruff and/or hair lossand/or canities, comprising the topical application to the skin or hairof a composition including, in a physiologically acceptable medium, atleast one DHEA derivative of formula (I) as defined above, alone or incombination with at least one compound as described above.

[0363] The present invention will now be illustrated by the followingnonlimiting examples. In the composition examples, the amounts areindicated as percentage by weight.

EXAMPLES Example 1 Moisturizing Cream

[0364] Phase A Acrylate/C₁₀₋₃₀ acrylate copolymer  0.5% Water 12.0%Phase B Hydrogenated polyisobutene  5.0% Androst-5-en-17-one,3-(acetyloxy)-7-  0.1% methoxy-, (3β, 7α) Cyclohexasiloxane  6.0% PhaseC Triethanolamine  1.0% Glycerol  6.0% EDTA  0.2% Preservatives  0.5%Glycine  2.0% Polyacrylamide and C₁₃₋₁₄ isoparaffin and  1.0% laureth-7Water q.s. for  100%

[0365] This composition can be prepared in the following way. Thepolymer of phase A is dispersed in water at 40° C. The constituents ofphase B are heated at 70° C. until completely dissolved and then thetemperature is brought back to 40° C. The constituents of phase C aremixed at 50° C. Phase B is subsequently introduced into phase A at 40°C. with stirring and then phase C is added to them.

[0366] The above composition makes it possible to remoisturize and tosmooth dry skin.

Example 2 Moisturizing Cream

[0367] The following composition is prepared in a way conventional to aperson skilled in the art. Phase A Demineralized water q.s. for  100%Preservatives  0.5% Carbomer  0.4% Glycerol  7.0% Phase B1Oxyethylenated (200 EO) sorbitan stearate  0.9% Phase B2 PEG-100stearate and glyceryl stearate  2.1% Isononyl isononanoate 10.0%Petroleum jelly  2.0% Octyldodecanol 10.0% Androst-5-en-17-one,3-(acetyloxy)-7-  0.5% methoxy-, (3β, 7α) Butylated hydroxytoluene  0.1%UV screening agent  1.0% Ceramides  0.5% Phase C Water  2.0%Triethanolamine  0.5% Urea  1.0%

[0368] This cream can be used for caring for dry skin.

Example 3 Antiageing Cream

[0369] Acrylate/C₁₀₋₃₀ acrylate copolymer  0.5% Water 12.0% Isononylisononanoate  5.0% Androst-5-ene-7,17-dione, 3-(acetyloxy),  0.1%17-oxime, (3β) Cyclohexasiloxane  5.0% Octyl methoxycinnamate  1.0%Triethanolamine  1.0% Glycerol  6.0% Preservatives  0.5% Polyacrylamideand C₁₃₋₁₄ isoparaffin and  1.0% laureth-7 Water q.s. for  100%

[0370] This composition can be prepared in the following way. Thepolymer of phase A is dispersed in water at 40° C. The constituents ofphase B are heated at 70° C. until completely dissolved and then thetemperature is brought back to 40° C. The constituents of phase C aremixed at 50° C. Phase B is subsequently introduced into phase A at 40°C. with stirring and then phase C is added to them.

[0371] This cream can be used in once or twice daily applications totreat cutaneous signs of ageing, in particular to fade out wrinkles andfine lines.

Example 4 Antiageing Cream

[0372] The following composition is prepared in a way conventional to aperson skilled in the art. Phase A Demineralized water q.s. for 100.0%Preservatives  0.5% Carbomer  0.4% Glycerol  7.0% Phase B1Oxyethylenated (200 EO) sorbitan stearate  0.9% Phase B2 PEG-100stearate and glyceryl stearate  2.1% Isononyl isononanoate  10.0%Octyldodecanol  10.0% Androst-5-ene-7,17-dione, 3-(acetyloxy),  0.1%17-oxime, (3β) Butylated hydroxytoluene  0.1% UV screening agent  1.0%Phase C Water  2.0% Triethanolamine  0.5% Extract of Centella asiatica 1.0% Palmitoyl pentapeptide (Matrixyl ® from  0.1% Sederma)

[0373] This cream is of use as firming day cream.

Example 5 Cleansing Gel for Greasy Skin

[0374] The following composition is prepared in a way conventional to aperson skilled in the art.: Lauryl phosphate  6.50% Decyl glucoside16.25% Polyquaternium-7  5.70% Oxyethylenated (150 EO) pentaerythrityl 0.50% tetrastearate Glycerol  3.50% Sorbitol  3.50% Potassium hydroxide 1.70% Hydroxypropylcellulose  0.20% Disodium EDTA  0.05% Sodiumchloride  0.10% Androst-5-en-17-One, 3-(acetyloxy)-7-  0.5% fluoro-,(3β, 7β) Preservatives  0.30% Water q.s. for   100%

[0375] This gel makes it possible to regulate sebum secretions and totone down skin imperfections.

Example 6 Antiblemish Patch

[0376] A patch comprising the following composition is prepared: Water40.0% Alcohol q.s. for  100% Glycerol  7.0% Androst-5-en-17-one,3-(acetyloxy)-7-  0.1% fluoro-, (3β, 7β) Poly (vinyl alcohol)  5.0%Kojic acid  0.5%

[0377] This patch can be applied to the hands and to the area above theneckline to fade out pigmentary blemishes, in particular blemishes dueto ageing.

Example 7 Hair Lotion for Combating Hair Loss

[0378] The following composition is prepared in a way conventional to aperson skilled in the art: Water 25.0% Glycerol  7.0%Androst-5-ene-7,17-dione, 3-(acetyloxy)-,  0.5% 17-oxime, (3β) Alcoholq.s. for  100%

[0379] This lotion is effective in preventing hair loss.

[0380] The present application claims priority from French patentapplication no. 0113817, filed Oct. 25, 2001, the entire disclosure ofwhich is hereby incorporated by reference. Also, all publications,patents and other documents disclosed herein are hereby incorporated byreference as well.

1. A method for improving the appearance of a keratinous substancecomprising applying to said keratinous substance at least one DHEAderivative of the following formula (I):

in which: R1 is selected from the group consisting of (a) a hydrogenatom; (b) a saturated or unsaturated, linear or branched, or cyclic,which can optionally comprise one or more heteroatoms, alkyl group whichis optionally substituted by one or more groups selected from the gropconsisting of —OR′, —SR′, —COOR′, —NR′R′, halogen, perfluoroalkyl,sulphate, phosphate, aryl, heterocycle, and mixtures thereof; (c) analkylcarbonyl group, the alkyl part of which is saturated orunsaturated, linear, branched or cyclic, and optionally substituted byone or more groups selected from the group consisting of —OR′, —SR′,—COOR′, —NR′R′, halogen, perfluoroalkyl, sulphate, or phosphate, aryl,heterocycle, and mixtures thereof; (d) a phenyl group, optionallysubstituted by one or more groups selected from the group consisting of—OR′, —SR′, —COOR′, —NR′R′, halogen, perfluoroalkyl, sulphate,phosphate, aryl, heterocycle groups, and mixtures thereof; (e) a benzylgroup, optionally substituted by —OR′, —SR′, —COOR′, —NR′R′, halogen,perfluoroalkyl, sulphate, phosphate, aryl, heterocycle groups, andmixtures thereof; (f) an arylcarbonyl group or an arylalkylcarbonylgroup optionally substituted by one or more groups selected from thegroup consisting of —OR′, —SR′, —COOR′, —NR′R′, halogen, perfluoroalkyl,sulphate, phosphate, aryl, heterocycle groups, and mixtures thereof; (g)an O═P(OH)OR′ group; (h) an (O)₂SOR′ group; (i) an (O)₂SR′ group; (j) atrialkylsilyl group (SiR₁₃) in which the R′ groups may be identical ordifferent; (k) an alkyloxycarbonyl group (R′OCO); (l) analkylaminocarbonyl group (R′NR′′′CO); and (m) a carbohydrate comprising3 to 100 carbon atoms; R4 and R5: (a) together represent a groupselected from the group consisting of (1) a keto group (═O); (2) a=CHR′group; (3) an=NR′ group; and (4) a=NCOR′ group; (b) each represent anidentical —OR″ group; (c) each represent an identical or different groupselected from the group consisting of (1) a hydrogen atom; (2) an —NR′R′group; and (3) an —NHCOR′ group; R2 and R3 are: (a) when R3 is ahydrogen atom, R2 is selected from the group consisting of (1) an —OR6group in which R6 has the same definitions as those given above for R1;(2) an amine group —N(R7)₂ in which the R7 substituents, which areidentical or different, have the same definitions as those given abovefor R1; (3) an N-sulphonamide group (—NR′′′SO₂R′) or an N-sulphonategroup (—NR′′′SO₃R′); (4) a urea group (—NR′′′CONR′R′); (5) an alkylamidegroup (—NR′′′COR′); (6) an N-carbamate group (—NR′′′COOR′); (7) a thiolgroup (—SR′); (8) a thiophenyl group (—SPh); (9) a sulphone group(—SO2R′); (10) a sulphoxide group (—SOR′); (11) a halogen; and (12) analkylsilane group (—SiR′3) in which the R′ groups may be identical ordifferent; (b) R2 and R3 together represent a group selected from thegroup consisting of (1) a methylene (═CHR′); (2) an imine (═NHR′); (3)an oxime (═NOR′); (4) a hydrazone (═N—NR′R′); and (5) a keto group (═O);(c) R2 and R3 each represent an —OR″ group in which each of the R″groups represents an alkyl group; R′ is selected from the groupconsisting of a hydrogen atom and a saturated or unsaturated, linear orbranched, or cyclic, which can optionally comprise one or moreheteroatoms, alkyl group optionally substituted by one or more —OR′′′,—COOR′′′, halogen, and —NR′′′R′′′ groups; or an aryl group, optionallysubstituted by one or more —OR′′′, —COOR′′′, halogen, and —NR′′′R′′′groups; R′′′ represents a hydrogen atom or a saturated or unsaturatedand linear, branched or cyclic alkyl chain; wherein in each of the—NR′R′ and —NR′′′R′′′ groups, the R′ and R′′′ substituents are identicalor different; with the exception of the DHEA derivatives of formula (I)for which: (a) R2 and R3 together represent a keto group; (b) R4 and R5together represent a keto group; and (c) R1 is as defined above; withthe exception of the DHEA derivatives of formula (A)

in which: R₁ is selected from the group consisting of a hydrogen atom,an ester of organic acid comprising 1 to 24 carbon atoms, a sulphuricester, a phosphoric ester, a carbonaceous ether comprising 1 to 24carbon atoms optionally comprising nitrogen atoms, and ethers ofcarbohydrates comprising 3 to 100 carbon atoms and their derivativesoptionally comprising nitrogen atoms; R₂ is selected from the groupconsisting of a hydrogen atom and an ester group of fatty acidcomprising 1 to 24 carbon atoms; R₃ is selected from the groupconsisting of a hydrogen atom, an —OH group, —CO—R₄, —CHOH—R₄, ═CH—CH₃,═COH—CH₃, —CHR₄—CH₃, and ═O, in which R₄ is an alkyl group comprisingfrom 1 to 10 carbon atoms which is optionally substituted.
 2. The methodaccording to claim 1, wherein the DHEA derivative comprises R1 which isa saturated or unsaturated, linear or branched, or cyclic, which canoptionally comprise one or more heteroatoms, C₁-C₁₂ alkyl groupoptionally substituted by one or more groups selected from the groupconsisting of —OR′, —SR′, —COOR′, —NR′R′, halogen, and mixtures thereof.3. The method according to claim 1, wherein the DHEA derivativecomprises R1 which is a saturated or unsaturated, linear or branched, orcyclic, which can optionally comprise one or more heteroatoms, C₁-C₆alkyl group optionally substituted by one or more groups selected fromthe group consisting of —OR′, —SR′, —COOR′, —NR′R′, halogen, andmixtures thereof.
 4. The method according to claim 1, wherein the DHEAderivative comprises R1 which is substituted with a heterocycle selectedfrom the group consisting of an indole, a pyrimidine, a piperidine, amorpholine, a pyran, a furan, a piperazine, and a pyridine;
 5. Themethod according to claim 1, wherein the DHEA derivative comprises R1which is a C₁-C₂₄ alkylcarbonyl group, the alkyl part of which issaturated or unsaturated and linear, branched or cyclic and optionallysubstituted by one or more groups selected from the group consisting of—OR′, —SR′, —COOR′, —NR′R′, halogen, and mixtures thereof.
 6. The methodaccording to claim 5, wherein R1 is an alkylcarbonyl group with a C₆-C₁₈alkyl part.
 7. The method according to claim 1, wherein the DHEAderivative comprises R1 which is a phenylcarbonyl or a benzylcarbonyl.8. The method according to claim 1, wherein the DHEA derivativecomprises R3 which is a hydrogen atom and R2 which is selected from thegroup consisting of (a) an —OR6 group in which R6 has the samedefinitions as those given for R1 in claim 1; (b) an amine group —N(R7)₂in which the R7 substituents, which are identical or different, have thesame definitions as those given in claim 1; (c) a thiol group (—SR′);and (d) a halogen.
 9. The method according to claim 1, wherein the R′and R′′′ groups are selected from the group consisting of a hydrogenatom and a C₁-C₆ alkyl group.
 10. The method according to claim 1,wherein the R′ and R′′′ groups are selected from the group consisting ofa hydrogen atom, a methyl group, an ethyl group, a butyl group, a propylgroup, an isopropyl group and a tert-butyl group.
 11. The methodaccording to claim 1, wherein the —NR′R′ and —NR′′′R′′′ groups are aminoacids.
 12. The method according to claim 11, wherein the —NR′R′ and—NR′′′R′′′ groups are selected from the group consisting of L-alanine,L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamine,L-glutamic acid, glycine, L-histidine, L-isoleucine, L-leucine,L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine,L-threonine, L-tryptophan, L-tyrosine or L-valine.
 13. The methodaccording to claim 1, wherein the DHEA derivative comprises R4 and R5which together form a 1,3-dioxolane ring or a 1,3-dioxane ring.
 14. Themethod according to claim 1, wherein the DHEA derivative comprises R3which is a hydrogen atom and R2 is an alkali metal salt of anN-sulphonamide group (—NR′′′SO₂R¹) or an N-sulphonate group(—NR′′′SO₃R¹).
 15. The method according to claim 1, wherein the DHEAderivative comprises R2 and R3 which are C₁-C₆ alkyl chains or whichtogether form a 5- or 6-membered ring.
 16. The method according to claim1, wherein the DHEA derivative of formula (I) is selected from the groupconsisting of (1) Androst-5-en-17-one, 3-(acetyloxy)-7-(benzoyloxy)-,(3β,7α); (2) Androst-5-en-17-one,7-hydroxy-3-[[(1-oxopentyl)sulphonyl]oxy]-, (3β,7β); (3)Androst-5-en-17-one, 3-hydroxy-7-(1-oxo-3-phenylpropoxy)-, (3β,7β); (4)Androst-5-en-17-one,7-hydroxy-3-[[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propenyl]oxy]-,(3β); (5) Androst-5-en-17-one,7-hydroxy-3-[[(9Z)-1-oxo-9-octadecenyl]oxy]-, (3β); (6)Pregn-5-en-20-one, 3-(acetyloxy)-7-hydroxy-, (3β,7αa); (7) Butanoicacid, 4-[[[(3β,7Z)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-;(8) Butanoic acid,4-[[[(3β,7Z)-3-(acetyloxy)-17-oxoandrost-5-en-7-ylidene]amino]oxy]-,methyl ester; (9) Androst-5-en-17-one,3-(benzoyloxy)-7-(2-methyl-1-oxopropoxy)-, (3β,7β); (10)Androst-5-en-17-one, 3-(acetyloxy)-7-fluoro-, (3β,7β); (11)Androst-5-en-17-one, 3-(acetyloxy)-7-fluoro-, (3β,7α); (12) Acetic acid,[[[(3β,7Z)-3-hydroxy-20-oxopregn-5-en-7-ylidene]amino]oxy]-; (13) Aceticacid, [[[(3β,7Z)-3-(acetyloxy)-20-oxopregn-5-en-7-ylidene]amino]oxy]-,methyl ester; (14) Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, (3β);(15) Androst-5-en-17-one, 7-bromo-3-hydroxy-, (3β,7α); (16)Androst-5-en-17-one, 7-bromo-3-hydroxy-, (3β); (17) Pregn-5-en-20-one,7-bromo-3-hydroxy-, acetate; (18) Pregn-5-en-20-one,3-(acetyloxy)-7-bromo-, (3β); (19) Pregn-5-en-20-one,7α-chloro-3β-hydroxy-, acetate; (20) Pregn-5-en-20-one,3-(acetyloxy)-7-bromo-, (3β,7β); (21) Pregn-5-en-20-one,3-(acetyloxy)-7-bromo-, (3β,7α) (22) Pregn-5-en-20-one,7-bromo-3-hydroxy-, benzoate; (23) Pregn-5-en-20-one,7-bromo-3β-hydroxy-, 4-methylvalerate; (24) Androst-5-en-17-one,3β,7α-dihydroxy-, disulphate; (25) Acetic acid,[[(3β,7α)-3-hydroxy-17-oxoandrost-5-en-7-yl]thio]-; (26)Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 7,17-dioxime, (3β); (27)Androst-5-en-17-one, 3-(benzoyloxy)-7-bromo-, (3,7α); (28) Acetic acid,[[[(3β,7Z)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-; (29)Acetic acid,[[[(3β,7Z)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-, methylester; (30) Acetic acid,[[[(3β,7Z)-3-(acetyloxy)-17-oxoandrost-5-en-7-ylidene]amino]oxy]-,methyl ester; (31) Androst-5-en-17-one, 3,7-bis[(trimethylsilyl)oxy]-,(3β,7β); (32) Androst-5-en-17-one,7-hydroxy-3-[[(3-methyl-phenyl)sulphonyl]oxy]-, (3β,7α); (33)Androst-5-en-17-one, 3-[(3-chlorobenzoyl)-oxy]-7-hydroxy-, (3β,7α); (34)Androst-5-en-17-one, 7-(3-carboxy-1-oxopropoxy)-3-[(1-oxoheptyl)oxy]-,(3β,7α); (35) Pregn-5-en-20-one, 3,7-bis[(trimethylsilyl)oxy]-, (3β,7α)(36) Androst-5-en-17-one, 3,7-bis[(trimethylsilyl)oxy]-, (3β,7α); (37)Acetic acid, [[[(3β)-3-hydroxy-17-oxoandrost-5-en-7-ylidene]amino]oxy]-;(38) Androst-5-en-17-one, 3-(acetyloxy)-7-methoxy-, (3,7α); (39)Androst-5-en-17-one, 3-(acetyloxy)-7-methoxy-, (3β,7β); (40)Pregna-5,16-diene-7,20-dione, 3-(acetyloxy)-, 7,20-dioxime, (3β); (41)Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, (3β,7α); (42)Pregn-5-en-20-one, 3β,7α-dihydroxy-, 7-(hydrogen sulphate); (43)Androst-5-en-17-one, 3-hydroxy-7-(sulphooxy)-, (3β,7α); (44)Pregn-5-ene-7,20-dione, 3-hydroxy-, bis[(aminoiminomethyl)hydrazone],(3β); (45) Guanidine,1,1′-[(3β-hydroxypregn-5-ene-7,20-diylidene)dinitrilo]di-,dihydrochloride; (46) Androst-5-en-17-one, 7-bromo-3β-hydroxy-,benzoate; (47) Androst-5-en-17-one, 3-hydroxy-7-methoxy-, (3β,7α); (48)Androst-5-en-17-one, 3-hydroxy-7-methoxy-, (3β,7β); (49)Androst-5-en-7-one, 3-(acetyloxy)-17-(benzoyloxy)-,7-[O-(phenylmethyl)oxime], (3β,7E,17β); (50) Androst-5-ene-3,7,17-triol,17-(hydrogen sulphate), (3β,7β,17β); (51) Androst-5-en-7-one,3,17-bis(acetyloxy)-, 7-[O-(3-hydroxypropyl)oxime], (3β,7Z,17β); (52)Propanoic acid,3-[[[(3β,7Z,17β)-3,17-bis(acetyloxy)androst-5-en-7-ylidene]amino]oxy]-,methyl ester; (53) Propanoic acid,3-[[[(3β,7Z,17β)-3,17-bis(acetyloxy)androst-5-en-7-ylidene]amino]oxy]-;(54) Androst-5-en-17-one,7-(acetyloxy)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, cyclic17-(1,2-ethanediyl acetal), (3β,7β); (55) Androst-5-en-7-one,3-(acetyloxy)-17-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, cyclic7-(1,2-ethanediyl acetal), (3β,17β); (56) Androst-5-ene-7,17-diol,3-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-, 17-octanoate, (3β,7β,17β);(57) Butanoic acid,4-[[[(3β,7Z,17β)-3-(acetyloxy)-17-hydroxyandrost-5-en-7-ylidene]amino]oxy]-,methyl ester; (58) Androst-5-ene-3,7,17-triol, 17-acetate 3-benzoate,(3β,7β,17β); (59) Acetic acid,[[[(3β,7Z,17β)-3-(acetyloxy)-17-hydroxyandrost-5-en-7-ylidene]amino]oxy]-,methyl ester; (60) Androst-5-ene-3,7,17-triol, 3,17-diacetate7-methanesulphonate, (3β,17β); (61) Androst-5-ene-3,17-diol, 7-bromo-,diacetate, (3β,7α,17β); (62) Androst-5-ene-3,7,17-triol, 3-acetate17-benzoate, (3β,7α,17β); (63) Androst-5-ene-3,7,17-triol, 3-acetate17-benzoate, (3β,7β,17β); (64) Androst-5-ene-3,17-diol, 7-bromo-,(3β,7α,17β); (65) Androst-5-ene-3,17-diol, 7-bromo-, (3β,17β); (66)Androst-5-ene-3,17-diol, 7-bromo-, 3-acetate 17-benzoate, (3β,7α,17β);(67) Androst-5-ene-3,17-diol, 7-(phenylsulphinyl)-, diacetate, (3β,17β);(68) Androst-5-ene-3,17-diol, 7-(phenylthio)-, diacetate, (3β,17β); (69)Androst-5-ene-3,17-diol, 7-bromo-, diacetate, (3β,17β); (70)Androst-5-ene-3β,17β-diol, 7-bromo-, dibenzoate; (71)Androst-5-ene-3,17-diol, 7-bromo-, 3-acetate 17-benzoate, (3β,7β,17β);(72) Propanoic acid,3-[[(3β,7α,17β)-3-(acetyloxy)-17-(benzoyloxy)androst-5-en-7-yl]thio]-,methyl ester; (73) Propanoic acid,3-[[(3β,7α,17β)-3,17-dihydroxyandrost-5-en-7-yl]thio]-; (74)Androst-5-en-7-one, 3-(acetyloxy)-17-(benzoyloxy)-,7-[O-(phenylmethyl)oxime], (3β,7Z,17β); (75) Androst-5-ene-3,7,17-triol,3-acetate 7,17-dibenzoate, (3β,7α,17β); (76) Androst-5-ene-3,7,17-triol,3-acetate 7,17-dibenzoate, (3β,7β,17β); (77) Androst-5-en-17-one,3-(acetyloxy)-7-bromo-, cyclic 1,2-ethanediyl acetal, (3β,7β); (78)Androst-5-en-7-one, 3-(acetyloxy)-17-(benzoyloxy)-,7-[O-(phenylmethyl)oxime], (3β,17β); (79) Androst-5-en-17-one,3,7-bis(acetyloxy)-, cyclic 17-(1,2-ethanediyl acetal), (3β,7α); (80)Androst-5-en-17-one, 3-(acetyloxy)-7-hydroxy-, cyclic 17-(1,2-ethanediylacetal), (3β,7β); (81) Androst-5-en-17-one, 3-(acetyloxy)-7-hydroxy-,cyclic 17-(1,2-ethanediyl acetal), (3β,7α); (82)Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 7,17-dioxime, (3β); (83)Androst-5-en-3-ol, 7-bromo-, benzoate, (3β); (84)Androst-5-ene-7,17-dione, 3-(acetyloxy)-, 17-(1,2-ethanediyl acetal),7-oxime, (3β,7Z); (85) Acetic acid,[[[(3β,7Z)-3-(acetyloxy)-17,17-[1,2-ethanediylbis(oxy)]androst-5-en-7-ylidene]amino]oxy]-,methyl ester; (86) Androst-5-en-7-one, 3,17-bis[(trimethylsilyl)oxy]-,O-methyloxime, (3β,17β); (87) Androst-5-en-7-one, 3,17-dihydroxy-,oxime, (3β,17β); (88) Androst-5-ene-7,17-dione, 3-(acetyloxy)-,17-oxime, (3β); (89) Androst-5-ene-7,17-dione, 3-(acetyloxy)-,7,17-dioxime, (3β); (90) Acetic acid,[[[(3β,17β)-3,17-dihydroxyandrost-5-en-7-ylidene]amino]oxy]-; (91)Acetic acid,[[[(3β)-17,17-[1,2-ethanediylbis(oxy)]-3-hydroxyandrost-5-en-7-ylidene]amino]oxy]-;(92) Silane,[[(3β,7α,17β)-androst-5-ene-3,7,17-triyl]tris(oxy)]tris[trimethyl]-;(93) Benzenesulphonic acid, 4-methyl-,[(3β,17β)-3,17-bis(acetyloxy)androst-5-en-7-ylidene]hydrazide; (94)Androst-5-en-7-one, 3,17-bis(acetyloxy)-, oxime, (3β,17β); (95)Androst-5-en-17-one, 3-(acetyloxy)-7-bromo-, cyclic 1,2-ethanediylacetal, (3β,7α); (96) Androst-5-en-17-one, 7-bromo-3-hydroxy-, cyclic1,2-ethanediyl acetal, (3β,7α); (97) Androst-5-en-3β-ol, 7α-bromo-,acetate; and (98) Androst-5-en-3β-ol, 7α-bromo-.
 17. The methodaccording to claim 1, wherein the method comprises preventing ortreating cutaneous signs of ageing.
 18. The method according to claim 1,wherein the method comprises preventing or treating a faded complexion.19. The method according to claim 1, wherein the method comprisespreventing or treating disorders of pigmentation of the skin or hair.20. The method according to claim 1, wherein the method comprisespreventing or treating sensitive skin and/or dandruff and/or drying ofthe skin.
 21. The method according to claim 1, wherein the methodcomprises preventing or treating hyperseborrhoea and/or imperfectionsrelated to hyperseborrhoea.
 22. The method according to claim 1, whereinthe method comprises preventing or treating hair loss and/or canities.23. The method according to claim 17, wherein the cutaneous signs ofageing are selected from the group consisting of wrinkles and finelines, cutaneous atrophy, loss of firmness and/or of elasticity of theskin, an uneven skin grain with presence of dilated pores, and loss ofradiance of the skin and/or pigmentary blemishes.
 24. A compositioncomprising, in a physiologically acceptable medium, at least one DHEAderivative according to claim 1 and at least one compound selected fromthe group consisting of a desquamating agent, a moisturizing agent, adepigmenting or propigmenting agent, an antiglycation agent, anNO-synthase inhibitor, a 5α-reductase inhibitor, a lysyl and/or prolylhydroxylase inhibitor, an agent which stimulates the synthesis of dermalor epidermal macromolecules and/or which prevents their decomposition,an agent which stimulates the proliferation of fibroblasts andkeratinocytes and/or the differentiation of keratinocytes, a musclerelaxant, a compound which reduces irritation of neurogenic origin, anantimicrobial agent, a tightening agent, an agent for combatingpollution or free radicals, and a soothing agent capable of inhibitingat least one enzyme.
 25. A cosmetic composition comprising, in aphysiologically acceptable medium, at least one DHEA derivativeaccording to claim 1 and at least one optionally coated inorganicpigment and/or at least one UV screening agent selected from the groupconsisting of (a) a benzophenone derivative; (b) a triazine derivative;(c) benzene-1,4-di(3-methylidenecamphor-10-sulphonic acid), optionallyin the partially or completely neutralized form; (d) a salicylic acidderivative; (e) a cinnamic acid derivative; (f) a liquidβ,β-diphenylacrylate derivative; (g) a p-aminobenzoic acid derivative;(h) 4-methylbenzylidenecamphor; (i) 2-phenylbenzimidazole-5-sulphonicacid; (j) a 1,3,5-triazine derivative; (k) a plant extract selected fromthe group consisting of an extract of Rosmarinus officinalis, ofLeontopodium alpinum of Leontopodium stracheyi; and mixtures thereof;and (l) a benzotriazole silicone of formula:


26. The composition according to claim 24, wherein 0.00001% to 10% byweight of the DHEA derivative with respect to the total weight of thecomposition is present.
 27. The composition according to claim 25,wherein 0.00001% to 10% by weight of the DHEA derivative with respect tothe total weight of the composition is present.
 28. The compositionaccording to claim 24, wherein from 0.001% to 5% by weight of the DHEAderivative with respect to the total weight of the composition ispresent.
 29. The composition according to claim 25, wherein from 0.001%to 5% by weight of the DHEA derivative with respect to the total weightof the composition is present.
 30. The composition according to claim24, wherein from 0.1% to 0.5 by weight of the DHEA derivative withrespect to the total weight of the composition is present.
 31. Thecomposition according to claim 25, wherein from 0.1% to 0.5% by weightof the DHEA derivative with respect to the total weight of thecomposition is present.